Cloning the Zika Virus - A Step Towards the Cure

Zika
is a vector-borne tropical disease, which has led to recent outbreaks in
several countries.

Till
date, there exists no cure or vaccine for the virus.

A
team of researchers have
successfully genetic engineered a clone of the Zika virus.

Cloning
the virus may be a major step towards the development of a vaccine against
the disease and for
therapeutic purposes.

Zika virus infection leads to flu like symptoms in adults but can lead to microcephaly (smaller head and brain) in new-born infants. The spread of this disease has reached epidemic proportions where people from Brazil, French Polynesia to America have found to be infected with this virus. Owing to this, WHO declared the disease as a Public Health Emergency of International Concern (PHEIC) on 1st February 2016.

No Cure or Vaccine for
Zika Virus

An
alarming factor associated with this disease is the absence of a cure or a
vaccine against the virus. Patients affected with this virus are treated
symptomatically.

New Study Brings Hope

This may not hold true for long, though, as a multidisciplinary team from Galveston, Texas has been successful in cloning the Zika virus, as revealed by a study
published in the journal Cell Host & Microbe.

Cloning the Zika Virus - A Step Towards the Cure

The feat has been accomplished by a team of researchers at the University of Texas Medical Branch at Galveston. There are two strains of Zika virus- the Asian and the African lineage. The Asian lineage is found to be more virulent than the African and is responsible for the current outbreak of Zika.

‘Genetic cloning of the Zika virus may be the first big breakthrough in the development of a vaccine against the disease.’

The
clinical isolate of the Zika virus used in the study was of Asian lineage and
taken from a 3 year old Cambodian. This was used as the template for cloning
the infectious cDNA clone. 5 fragments that covered the entire viral genetic
sequence were cloned and assembled into the full-length
clone. This newly synthesized cDNA was termed pfLZIKV.

Infectivity of the New
Clone

Cell
Lines:

The pfLZIKV
RNA transcript was used to transfect vero cells to determine the infectious
nature of the clone. Cytopathic effects were noticed in the transfected cells,
displaying infectivity. Vero cells are cell lineages used in cell cultures.

Injection
into Mice:

When
the cloned DNA was injected into laboratory mice A129 (which lacked α/β
interferon), there was weight loss on the first day and greater indication of
virulence on the second and the third day.

Injection
of the cloned DNA into mice with no αβ and γ interferons showed neurological
symptoms.

Infection and Spread of
Cloned Zika Virus

After
this, the researchers used the cloned virus to infect artificial human blood
and allowed Aedes aegypti mosquitoes
to feed on it. After 14 days post feeding the mosquitoes were tested for the
presence of the virus in their legs as well as bodies. The cloned virus showed
greater infection and dissemination than the original virus. Apart from the
infective ability demonstrated by the newly cloned virus, this experiment
showed that A.aegypti was highly effective in transmitting this virus and
spreading disease.

These
tests are an indication that the cloned DNA was infectious and could be
transmitted by Aedes aegypti like the wild type strain and so can be
used for experimental studies.

Luciferase Signal and
Use in Drug Discovery

The
scientists included the Renilla luciferase gene into the cloned DNA as it can
act as an indicator of growth. When this recombinant DNA was transfected into
vero cells, luciferase signals were detected. This can be used to detect
antiviral drug discovery, as the signals will be absent if the drug works on
the transfected cells.

Luciferase
is the enzyme that causes fireflies to glow. This tracker can help in keeping a
track of the virus when introduced into mosquitoes and even aid the screening
of potential antivirals.

The
Significance of Cloning Zika Virus

Zika virus is a Flavivirus and is closely related to viruses that cause dengue fever and West Nile fever. Zika was initially transmitted from one monkey to another through a mosquito bite. It made its first appearance in humans in 1952 in Uganda and remained limited to the African continent. In 2007, after the increase in travel and trade across the world, the virus resulted in outbreaks in countries outside Africa.

Zika causes symptoms like fever, muscle and joint pains, rashes,
and conjunctivitis, which last around 2-7 days. Earlier, the rates of hospitalization due to the illness were low but lately, it has been associated with birth defects like microcephaly and serious illnesses like Guillain-Barre Syndrome (immune system disorder which causes weakening of the muscles and paralysis).

The change in its severity, mutation and
the unavailability of a drug or vaccine make this study a major breakthrough.
The cloned virus is genetically similar to the strain that is currently
prevalent in the United States of America.

The virus has undergone
mutation over the years which has made it more infectious for mosquitoes
and thus results in a faster spread of the disease. This can be
investigated by comparing the infectivity of the current strains with the
old ones. The chikungunya virus is a mutation of the Zika virus.

The evolution of the virus has
resulted in higher concentration in the infected individual's bloodstream
and is,
therefore, able to cross over to the fetus in the womb and causes birth defects.

The increased spread of the Zika virus is largely due to the nascent population, who have been unexposed to Zika or associated infections and who do not have the necessary anti-bodies to fight the disease. To understand the virulence and the spread of the disease an effective recombinant DNA with a marker will aid in study and drug trial. In the words of the lead author Pie-Yong Shi "The new Zika clone, together with mosquito infection models and the UTMB-developed Zika mouse model, represent a major advance towards deciphering why the virus is tied to serious diseases. The new clone is also a critical step in developing a vaccine and anti-viral drug against Zika."

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